HazMat Fee +
There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
| Type | HazMat fee for 500 gram (Estimated) |
| Excepted Quantity | USD 0.00 |
| Limited Quantity | USD 15-60 |
| Inaccessible (Haz class 6.1), Domestic | USD 80+ |
| Inaccessible (Haz class 6.1), International | USD 150+ |
| Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
| Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 3-Nitropyrazole
CAS No.: 26621-44-3
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only! Not for Human Use. We Do Not Sell to Patients.
Change View
| Size | Price | VIP Price |
DE Stock US Stock |
Asia Stock Global Stock |
In Stock |
| {[ item.pr_size ]}{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.p_spot_brand_remark ]} 1-2 weeks {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock Inquiry - | Login - + |
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ item.p_spot_brand_remark ]}
1-2weeks
Inquiry
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
Asia Stock: Ship in 3-5 business days
EU Stock: ship in 0-1 business day
Global Stock: ship in 7-10 days
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
| CAS No. : | 26621-44-3 |
| Formula : | C3H3N3O2 |
| M.W : | 113.07 |
| SMILES Code : | C1=C([N+]([O-])=O)[NH]N=C1 |
| English Name : | 3-Nitro-1H-pyrazole |
| MDL No. : | MFCD00159621 |
| InChI Key : | MZRUFMBFIKGOAL-UHFFFAOYSA-N |
| Pubchem ID : | 123419 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
| Num. heavy atoms | 8 |
| Num. arom. heavy atoms | 5 |
| Fraction Csp3 | 0.0 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 27.41 |
| TPSA ? Topological Polar Surface Area: Calculated from |
74.5 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.21 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.38 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.32 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.8 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.86 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.15 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.18 |
| Solubility | 7.52 mg/ml ; 0.0665 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.51 |
| Solubility | 3.49 mg/ml ; 0.0309 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.56 |
| Solubility | 31.2 mg/ml ; 0.276 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.72 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.92 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | In benzonitrile; for 2h;Reflux; | A solution of 1 -nitro-1 H-pyrazole (4.23 gm, 37.4 mmol; Oakwood Products, Inc., West Columbia, SC) in benzonitrile (42 ml_) was heated to reflux for 2 hours. After cooling to 45 0C, the reaction mixture, which was starting to precipitate, was poured into 175 ml_ hexanes. A white solid precipitated. This was collected by vacuum filtration, rinsed repeatedly with hexane and dried under high vacuum to afford 3.85 grams (91 percent) of (l-27a) as a white solid; 1H NMR (400 MHz, DMSO-d6) delta 13.90 (1 H), 8.01 (1 H), 7.01 |
| 91% | In benzonitrile; at 180℃; for 3h; | Example 15Preparation of 3-(4-fluorophenylsulfonyl)-N-(5-methoxy-lH-pyrazol-3- vDisoq uinolin- 1-amine[00264] Step A: A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180 °C for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-lH-pyrazole as a tan solid (3.16 g, 91percent). 1H NMR (300 MHz, DMSO-t/e) delta 13.94 (br s, 1H), 8.03 (d, J= 2.4 Hz, 1H), 7.03 (t, J= 2.4 Hz, 1H). |
| 91% | In benzonitrile; at 180℃; for 3h; | Step A: A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180° C. for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-1H-pyrazole as a tan solid (3.16 g, 91percent). 1H NMR (300 MHz, DMSO-d6) delta 13.94 (br s, 1H), 8.03 (d, J=2.4 Hz, 1H), 7.03 (t, J=2.4 Hz, 1H). |
| 91% | With benzonitrile; at 180℃; for 3h; | A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180 °C for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-lH-pyrazole as a tan solid (3.16 g, 91percent). H NMR (300 MHz, DMSO- 6) delta 13.94 (br s, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.03 (t, J = 2.4 Hz, 1H). |
| 79% | In benzonitrile; for 2h;Reflux; | Example 5 (S)-3-Cyclopentyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent): H1-NMR (400 MHz, DMSO-d6) delta 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
| 79% | In benzonitrile; for 2h;Reflux; | A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in benzonitrile (40 mL) was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent). 1H-NMR (400 MHz, DMSO-d6) delta 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). Intermediate 2. |
| 79% | In benzonitrile; for 2h;Heating / reflux; | A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into 160 mL of hexanes. A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent). H1-NMR (400 MHz, DMSO-d6) delta: 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
| 79% | In benzonitrile; for 2h;Heating / reflux; | Example 15 (E)-4-{3-[2-(3-Chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-Nitro-1H-pyrazole (3.16 g, 79percent): H1-NMR (400 MHz, DMSO-d6) delta7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
| 56% | at 145℃; for 10h; | N-Nitropyrazole (2 g, 18 mmol) was heated at 145 °C for 10 h in a round-bottom flask. Then the product was purified by silica column chromatography using 5:95 v/v methanol/chloroform as eluent to afford 56percent of 3(5)-<strong>[7119-95-1]nitropyrazole</strong> as a white solid. |
| 51% | In methoxybenzene; at 145℃; | 1-Nitropyrazole (10 g, 88 mmol) was heated in 600 ml of anisole at 145°C overnight. The mixture was cooled in a freezer which caused a precipitate to form. The precipitate was collected to give 5.075 g of the title compound as a tan solid (51percent). [M+H] calc'd for C3H3N3O2, 114; found, 114. |
| In methoxybenzene; at 145℃; | 3-Nitro-lH-pyrazolew; [539] [Ref.: Janssen, J.W.A.M. and Habraken, C.L., J. Org. Chem., 1971,36,3081.] A solution of l-nitro-ll/'-pyrazole (3.0g, 0.026 mol) in anisole (200mL) was heated at 145°C overnight. The mixture was cooled to rt, the white solid was collected by filtration and washed with hexanes. The mother liquid was diluted with hexanes (500mL) and cooled to -20°C, and the resulting off-white solid was collected and combined with the previous solid.LC-MS (ES, Pos.): 1 14 [MH+]. 'H NMR (DMSO-d6, 400 MHz): 5 = 7.04 (d, J= 2.5 Hz, 1H),8.04 (d, /= 2.5 Hz, 1H), 13.96 (br s, 1H). | |
| In benzonitrile; at 180℃; for 3h; | A solution of 1.0 g of <strong>[7119-95-1]N-<strong>[7119-95-1]nitropyrazole</strong></strong> in 10 mL of benzonitrile was heated for 3 h at 180 °C, after cooling the reaction mixture was poured into 30 mL of hexane. 3-<strong>[7119-95-1]nitropyrazole</strong> was collected by filtration. The crude yield after washing with hexane and drying was 0.93 g (98percent). The solid was recrystallized from water. m.p. 174?175 °C. FT-IR (KBr, cm?1) 3180 (N?H), 1520 and 1351 cm?1 (NO2). 1H NMR (DMSO-d6) delta: 7.96 (d, 1, 5(3)-H), 6.96 (d, 1, 4-H). EI-MS: m/z 113 (M+·). Anal. Calcd for C3H3N3O2: C, 31.86; H, 2.67; N, 37.16. Found: C, 32.19; H, 2.84; N, 37.18. | |
| at 180℃; | A 100mL one-neck flask equipped with a magnetic stirrer was added 5g of compound 1 and 15mL acetic acid, stirred, to give a clear solution. Under ice bath 3.5mL of fuming nitric acid was slowly added dropwise to the mixed solution, maintaining vigorous stirring, the reaction temperature does not exceed 30 deg. C. 10mL acetic anhydride was added to the mixture, after the addition, the mixture immediately became cloudy, to give a white turbid liquid. After the addition it was stirred at room temperature, until the solution became clear, about 2.5h. After completion of the reaction, the solution was slowly poured into 100mL crushed ice and with vigorous stirring, potassium carbonate was added portionwise until the mixture was neutral, white precipitate was filtered to give 5.6g of white powdery crystals, the filtrate was extracted with ethyl acetate, the combined organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation to give pale yellow crystals 1.3490g, total crude was 6.9490g, yield 91.9percent recrystallized from benzene. Weigh three 100mg compound 2 into thick-walled pressure bottle, gradually heated to 160 deg. C, 180 deg. C, 200 deg. C, the reaction at this temperature for 1 ~ 3h to obtain compound 3, the results shown in Table 1. | |
| In benzonitrile; at 180℃; for 3.5h; | <strong>[7119-95-1]N-<strong>[7119-95-1]nitropyrazole</strong></strong> is dissolved in benzonitrile, heated to 180 ° C, incubated for 3.5 h,cooled to 50-60 ° C after completion of thereaction, and added to n-hexane to make 3-nitrate The pyrazole is precipitated, filtered and dried to give 3-<strong>[7119-95-1]nitropyrazole</strong>; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 80.3% 2: 3.6% | With potassium hydroxide In diethyl ether; ethanol at 40℃; for 0.75h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 39% | In sodium hydroxide at 30℃; for 1h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium carbonate; In N,N-dimethyl-formamide; | Step 1c Preparation of the Nitropyrazole 4. 3-Nitropyrazole (1.13 g, 10 mmol) in dry DMF (10 ml), under argon, was treated with anhydrous K2CO3 (2.7 g, 15 mmol) and then, dropwise, with methyl-4-bromobutyrate (1.82 g, 10.05 mmol) at RT. After stirring overnight the DMF was removed and the residue partitioned between H2O and EtOAc. The combined organic extracts were washed (H2O and brine), dried (Na2SO4), filtered and evaporated to give a mixture of 4 and 6 (2.05 g) as a pale yellow oil. MS (ES+) m/z 214 (MH+). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 63% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 25℃; for 0.333333h; Stage #2: N-(3-(bromomethyl)phenyl)acetamide In N,N-dimethyl-formamide at 25℃; for 0.333333h; | 30 3-Nitro-1H-pyrazole (prepared as in Example 15, 1.24 g, 11.0 mmol) was dissolved in anhydrous N,N-dimethylformamide (25 mL) and a 60% suspension of sodium hydride in mineral oil (426 mg, 11.55 mmol) was added. The mixture bubbled and stirred at 25° C. for 20 min. N-(3-Bromomethyl-phenyl)-acetamide (1.5 g, 5.26 mmol) was added and the mixture continued to stir at 25° C. for 20 min. The mixture was diluted with ethyl acetate, washed with water, a saturated brine solution, dried over magnesium sulfate and concentrated in vacuo to a yellow oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded the desired product, N-[3-(3-nitro-pyrazol-1-ylmethyl)-phenyl]-acetamide (1.81 g, 63% yield) as an off white solid: H1-NMR (400 MHz, DMSO-d6) δ 2.01 (3H, s), 5.42 (2H, s), 6.96 (1H, d, J=7.9 Hz), 7.06 (1H, d, J=2.4 Hz), 7.27 (1H, t, J=7.8 Hz), 7.45 (1H, s), 7.52 (1H, d, J=7.9 Hz), 8.12 (1H, d, J=2.4 Hz), 9.93 (1H, s). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 6h; | 49 (S)-2-[4-(2-Chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic A solution of 3-nitro-1H-pyrazole (prepared as in Example 5, 12.0 g, 106 mmol) in N,N-dimethylformamide (150 mL) was treated with para-toluenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl ester (25.5 g, 89.0 mmol), and potassium carbonate (24.5 g, 178 mmol). The reaction mixture was heated to 90° C. for 6 h under nitrogen. After this time, the reaction mixture was diluted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. Purification by ISCO flash chromatography (128 g, 5-30% ethyl acetate/hexanes) afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-3-nitro-1H-pyrazole (14.5 g, 73%) as a light yellow oil. |
| 73% | With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 6h; Inert atmosphere; | I.1; 3 A solution of 3-nitro-1H-pyrazole (Intermediate 2, 12.0 g, 106 mmol) in N,N-dimethylformamide (150 mL) was treated with para-toluenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (25.5 g, 89.0 mmol), and potassium carbonate (24.5 g, 178 mmol). The reaction mixture was heated to 90° C. for 6 h under nitrogen. After this time, the reaction mixture was diluted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (ISCO 120 g, 5-30% ethyl acetate/hexanes) afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-3-nitro-1H-pyrazole (14.5 g, 73%) as a light yellow oil; ESI-LRMS m/e calcd for C9H13N3O4 [M+H+] 228, found 228 [M+H+]. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 23% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 12h; | Synthesis of tert-butyl 4-(3-nitro-1H-pyrazol-1-yl)piperidine-1-carboxylate (12) To a stirred solution of tert-butyl 4-hydroxypiperidine-1-carboxylate 10 (8.90 g, 44.21 mmol) and 3-nitro-1H-pyrazole 11 (5.00 g, 44.21 mmol) in THF (80 ml) was added TPP (17.3 g, 65.99 mmol) and followed by dropwise addition of DEAD (10.3 mL, 65.97 mmol) at room temperature. The reaction mixture was further stirred at room temperature for 12 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (50 mL) and extracted with ethyl acetate (2*50 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by silica gel column chromatography eluting with 0-30% ethyl acetate in n-hexane to afford 3.00 g (23% yield) of the title compound 12 as colorless oil. Reaction was monitored by TLC(LC system: 50% ethyl acetate in n-hexane; Rf=0.4) |
| 17% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 25℃; Inert atmosphere; | 4.19.a a) DIAD (5.22 rnL, 26.53 mmol) was added dropwise to a stirred solution of 3-nitro- lH-pyrazole (2 g, 17.69 mmol), tert-butyl 4-hydroxypiperidine-l-carboxylate (3.56 g, 17.69 mmol) and triphenylphosphine (5.80 mL, 26.53 mmol) in THF (30 mL) cooled to O0C under an atmosphere of nitrogen. The resulting solution was stirred at 00C for 10 minutes and then allowed to warm to room temperature and stirred overnight. The mixture was diluted with isohexane (80 mL) and EtOAc (20 mL) and stirred vigorously. The mixture was filtered and the residue washed with isohexane (20 mL). The combined filtrates were evaporated and the residue purified by chromatography on silica, eluting with a gradient of 20-100% EtOAc in isohexane. Fractions containing product were combined and evaporated to afford tert-butyl 4-(3-nitropyrazol-l-yl)piperidine-l-carboxylate (0.874 g, 17% yield); 1H NMR spectrum (300 MHz, DMSO): δ 1.42 (9H, s), 1.77 - 1.83 (2H, m), 2.04 - 2.09 (2H, m), 2.87 - 2.93 (2H, m), 4.04 - 4.09 (2H, m), 4.49 - 4.55 (IH, m), 7.07 (IH, d), 8.13 (IH, d); Mass spectrum: m/z (ESI+) (M-Φu+H)+ = 240.98 |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With caesium carbonate; In acetonitrile; at 80℃; for 2h;Inert atmosphere; | 6-(3-Nitro-pyrazol-1-yl)-hexan-2-oneIn a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a suspension of 5-nitro-1H-pyrazole (3.69 g, 29.35 mmol) and Cs2CO3 (10.53 g, 32.28 mmol) in AcCN (34.0 mL) was treated with a solution of 6-bromo-hexan-2-one (5.78 g, 32.28 mmol) in AcCN (26.0 mL). The reaction mixture was stirred at 80 C. for 2 h. Water (123 mL) and EA (185 mL) were added to the cooled reaction mixture. The aq. layer was extracted with EA (185 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound. TLC: rf (50:50 hept-EA)=0.21. LC-MS-conditions 02: tR=0.82 min; [M+H]+=212.28. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With potassium iodate; sulfuric acid; iodine In tetrachloromethane; water; acetic acid at 80 - 85℃; for 21h; | |
| 82.1% | With potassium iodate; sulfuric acid; iodine In tetrachloromethane; water at 66℃; for 3h; | |
| 20% | With N-iodo-succinimide In N,N-dimethyl-formamide at 90℃; Inert atmosphere; | 3 Example 1 4-chloro-3-nitro -1H-pyrazole (intermediate 2a) preparation General procedure: Added to the reaction bottle 3-nitro -1H-pyrazole (5mmol), NBS (5.5mmol), adding 20mLDMF (N, N-dimethyl formamide), then heating to 90 °C, under the protection of nitrogen reaction sleepovers. After the reaction is complete, most of the DMF is removed by reduced pressure distillation, solid precipitating a large amount of water, filtering, 20 ml water washing, to obtain the target product solid after drying, light yellow solid. (Yield 87%) |
| 83.5 %Spectr. | With potassium iodate; sulfuric acid; potassium iodide In tetrachloromethane; water at 66℃; for 3h; | |
| With N-iodo-succinimide In N,N-dimethyl-formamide at 55℃; for 12h; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 51% | With caesium carbonate In 1,4-dioxane at 120℃; for 0.5h; microwave irradiation; | 256 3-Nitro-lH-pyrazole (3 g, 26.5 mmol, 1 eq) , 3-chloro-l- methoxy-2-propanol (3.92 g, 31.9 mmol, 1.2 eq) , potassium iodide (5 mg, cat.), and cesium carbonate (17.2 g, 53.1 mmol, 2 eq) were mixed in 1,4-dioxane (18 ml). The mixture was subjected to microwave irradiation at 1200C for 30 min. The mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified with silica gel column chromatography using 10-60% ethyl acetate in hexane as an eluent to give 2.74 g of the title compound (51%) as a yellow oil. [M+H] calc'd for C7HnN3O4202, found 202. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 16.17h; | 1 Step 1: l-Isopropyl-3-nitro-lH-pyrazole Into a 250-mL round-bottom flask was placed a solution of 3-nitro-lH-pyrazole (10 g, 88.4 mmol) in DMF (100 mL). This was followed by the addition of NaH (60% wt, 3.9 g, 97.5 mmol) in portions at 0°C. The resulting solution was stirred for 0.5 h at 0°C. This was followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0°C in 10 min. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x100 mL of ethyl acetate. The organic layers were combined and dried over anhydrous Na2S04, then concentrated under vacuum. The residue was applied onto a silica gel column and eluted with a gradient of ethyl acetate/petroleum ether (1 :5 to 1 :3). This resulted in 11.8 g (86%) of the title compound as yellow oil. MS-ESI: 156.1 (M+l). |
| 86% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16.1667h; | 1 Step 1: 1-Isopropyl-3-nitro-1H-pyrazole Into a 250-mL round-bottom flask, was placed a solution of 3-nitro-1H-pyrazole (10 g, 88.4 mmol) in DMF (100 mL). This was followed by the addition of NaH (60% wt. oil dispersion, 3.9 g, 97.5 mmol) in portions at 0°C. The resulting solution was stirred for 0.5 h at 0°C. Thiswas followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0°C in 10 mm. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x100 mL of ethyl acetate. The organic layers were combined and dried over anhydrous Na2SO4, and then concentrated under vacuum. The residue was eluted from silica gel and eluted with a gradientof ethyl acetate/petroleum ether (1:5 to 1:3). This resulted in 11.8 g (86%) of the title compound as yellow oil. MS-ESI: 156.1 (M+1). |
| 86% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 16h; | 1 Step 1: 1-Isopropyl-3-nitro-1H-pyrazole Into a 250-mL round-bottom flask, was placed a solution of 3-nitro-1H-pyrazole (10 g, 88.4mmol) in DMF (100 mL). This was followed by the addition of NaH (60%, 3.9 g) in portions at0°C. The resulting solution was stirred for 0.5 h at 0°C. This was followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0°C in 10 mm. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. |
| 86% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; | 1 Step 1 : 1 -Isopropyl-3 -nitro-lH-pyrazole Into a 250-mL round-bottom flask, was placed a solution of 3 -nitro-lH-pyrazole (10 g, 88.4 mmol) in DMF (100 mL). This was followed by the addition of NaH (60%, 3.9 g) in portions at 0°C. The resulting solution was stirred for 0.5 h at 0°C. This was followed by the addition of 2- bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0°C in 10 min. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x100 mL of ethyl acetate and the organic layers combined and dried over anhydrous Na2S04, then concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1 :5 to 1 :3). This resulted in 11.8 g (86%) of the title compound as yellow oil. MS-ESI: 156.1 (M+l ). |
| 86% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide at 0 - 20℃; for 16h; | |
| 78% | With sodium hydride In N,N-dimethyl-formamide at 0 - 100℃; for 2h; regioselective reaction; | |
| 73% | Stage #1: 3-nitro-1H-pyrazole With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide at 20℃; for 12h; | 14 3-Nitro-1H-pyrazole xxxiii (5 g, 44.2 mmol) is dissolved in dimethylformamide (50 mL) and cesium carbonate (14 g, 43 mmol) is added. The reaction is stirred for thirty minutes at room temperature, and isopropyl bromide (5 mL, 53.3 mmol) is added. The reaction is stirred at room temperature for 12 hours, after which wafter (100 mL) is added and the reaction mixture is stirred for 10 minutes. The mixture is extracted into ethyl acetate (3 x 100 mL), and the organic layer is washed with brine and concentrated prior to purification by flash column chromatography (20% ethyl acetate in hexanes) to give xxxiv in 73% yield.;1] |
| 71% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 25℃; for 12h; | A Step A: i-Isopropyl-3-nitro-iH-pyrazole To a mixture of 3-nitro-iH-pyrazole (30 g, 265.31 mmol, 1 eq) in DMF (300 mL) was added NaH (11.14 g, 278.58 mmol, 60% purity in mineral oil, 1.05 eq) in portions at o °C. Then the reaction mixture was stirred at o °C for 0.5 hour. 2-Bromopropane (39.16 g, 318.37 mmol, 1.2 eq) was added and the resulting mixture was warmed to 25 °C for 12 hours. The reaction mixture was quenched with water (500 mL) and extracted with EtOAc (3 x 300 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by chromatography (Si02, petroleum ether: ethyl acetate, 50:1 to 2:1) to give the title compound (29.2 g, 71 %) as a yellow oil. (0810) NMR (400 MHz, CDCI3) d 749 (d, 1 H), 6.90 (d, 1 H), 4-634-56 (m, 1 H) and 1.58 (d, 6 H). |
| 58% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 15.5h; Inert atmosphere; | A Step A: 1-Isopropyl-3-nitro-1H-pyrazole To a solution of 3-nitro-1H-pyrazole (75 g, 663.3 mmol, 1 eq) in anhydrous DMF (500 mL) was added NaH (29 g, 729.6 mmol, 60% purity in mineral oil, 1.1 eq) under nitrogen at 0 °C. The reaction mixture was stirred for 30 minutes.2-Bromopropane (98 g, 795.9 mmol, 1.2 eq) was added. Stirring was continued at 0 °C for 30 minutes under nitrogen. The ice bath was removed and the reaction mixture was stirred at 20 °C for 15 hours. The resulting mixture was quenched with water (500 mL) and extracted with ethyl acetate (2 L). The organic layer was washed with water (2 × 500 mL) and brine (2 × 500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, petroleum ether: ethyl acetate, 50:1 to 5:1) to give the title compound (60 g, 58 %) as a white solid. 1H NMR (400 MHz, CDCl3) d 7.49 (d, 1 H), 6.82 (d, 1 H), 4.59-4.46 (m, 1 H) and 1.51 (d, 6 H). |
| 43.73% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 15℃; for 12h; Inert atmosphere; | A Step A: 1-isopropyl-3-nitro-1H-pyrazole To a solution of 3-nitro-1H-pyrazole (25 g, 221.09 mmol, 1 eq) in DMF (300 mL) was added NaH (10.61 g, 265.31 mmol, 60 wt.% in mineral oil, 1.2 eq) at 0 °C under N2. The suspension was stirred at 0 °C for 0.5 hour, then 2-bromopropane (27.19 g, 221.09 mmol, 1 eq) was added dropwise to the reaction mixture at 0 °C. The reaction mixture was stirred at 15 °C for 12 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution (200 mL), diluted with water (500 mL) and extracted with EtOAc (3 × 500 mL). The organic phases were washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromotography (SiO2, Petroleum ether: Ethyl acetate, 1:0 to 5 :1) to give the title compound (15 g, 43.73% yield) as a yellow oil.1H NMR (400 MHz, CDCl3): d 7.49 (d, 1 H), 6.89 (d, 1 H), 4.65-4.54 (m, 1 H) and 1.57 (d, 6 H). |
| 23% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide at 20℃; | 4.1 (1) 1-Isopropyl-3-nitro-1H-pyrazole3-Nitro-1H-pyrazole (1050 mg, 9.2 mmol), NaH (446 mg, 11.1 mmol) were dissolved in DMF (5 mL), the reaction system was stirred at 0 °C for 0.5 h,2-Bromopropane (1250mg, 10.2mmol) was added to the reaction system, the reaction system was stirred overnight at room temperature, quenched by adding a small amount of water, the mixture was extracted with ethyl acetate, and the organic phase was washed with saturated brine successively, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by reverse phase column to obtain 1-isopropyl-3-nitro-1H-pyrazolo[2,3-b]pyridine (320 mg, yield: 23%) |
| 54.7 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; | Step 1: 3-nitro-l-(propan-2-yl)-lH-pyrazole To a solution of 3-nitro-lH-pyrazole (5 g, 44.2 mmol) in DMF (50 mL) was added NaH (1.95 g, 48.6 mmol, 60% dispersion in mineral oil) in small portions at 0 °C and the mixture was stirred at r.t. for 0.5 hr. To the above mixture, 2-bromopropane (5.0 mL, 53 mmol) was added at 0 °C and the resulting mixture was stirred at r.t. overnight. The reaction mixture was poured into ice-water and extracted with MTBE (4 x 50 mL). The combined organic layers were washedwith brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 35% EtOAc in PE) to give the title compound (3.75 g, 54.7% yield) as yellow solid. LC/MS (ESI) m/z: 156 (M+H)+. |
| 54.7 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; | Step 1: 3-nitro-l-(propan-2-yl)-lH-pyrazole To a solution of 3-nitro-lH-pyrazole (5 g, 44.2 mmol) in DMF (50 mL) was added NaH (1.95 g, 48.6 mmol, 60% dispersion in mineral oil) in small portions at 0 °C and the mixture was stirred at r.t. for 0.5 hr. To the above mixture, 2-bromopropane (5.0 mL, 53 mmol) was added at 0 °C and the resulting mixture was stirred at r.t. overnight. The reaction mixture was poured into ice-water and extracted with MTBE (4 x 50 mL). The combined organic layers were washedwith brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash chromatography (silica gel, 0 - 35% EtOAc in PE) to give the title compound (3.75 g, 54.7% yield) as yellow solid. LC/MS (ESI) m/z: 156 (M+H)+. |
| 88 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydrogencarbonate In acetonitrile at 0 - 30℃; Stage #2: isopropyl bromide In acetonitrile at 50℃; | 1-2 Example 1 The present embodiment synthesizes 1-isopropyl-3-nitropyrazole, and its technical route is as follows:The steps are as follows: Add 950mL of acetonitrile into a 1L three-necked flask at room temperature (15-30°C), start stirring, add 95g of 3-nitropyrazole and 300g of sodium bicarbonate, stir well, cool in an ice bath to 0-5°C, slowly Slowly add 124g of 2-bromopropane dropwise, after the drop is complete, raise the temperature to 50°C and react for 20 hours, follow the reaction to completion by TLC, cool again, add water, then extract with ethyl acetate, combine the organic phases, wash with saturated brine, and concentrate the organic phases To dryness, the obtained solid was pulped with petroleum ether, filtered, and dried to obtain 115 g of 1-isopropyl-3-nitropyrazole, yield: 88%, purity: 98%. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With tetrabutylammomium bromide; potassium carbonate In acetone at 20℃; for 5h; | Prepared according to general procedure 4 with K2CO3 (4.47 g, 32.3 mmol), 4-difluoromethoxybenzyl chloride (1.25 mL, 6.47 mmol), 5-nitro-1 H-pyrazole (731 mg, 6.47 mmol), and Bu4NBr (425 mg, 1.29 mmol) in acetone (45 mL). The reaction is complete after 5 h at rt. Purification of the crude by automated FC (Buchi, EtOAc / heptane 1 :99→ 5:95→ 10:90→ 15:85→ 25:75 → 35:65, 20 g silicagel, flow 20 mL/min) yields the title compound. LC-MS: tR = 0.85 min (conditions 3). General procedure 4 for the N-alkylation of 5-nitro-1H-pyrazole. K2CO3 or NaH is added to a sol. of 5-nitro-1 H- pyrazole in acetone or DMF or THF. The mixture is stirred for 15-30 min. The desired electrophile and Bu4NBr are added. The mixture is stirred efficiently at rt until the reaction is complete. The mixture is optionally filtered (if K2CO3 is used) or quenched with water (if NaH is used), and the filtrate is evaporated under reduced pressure. The residue is partitioned between water and EtOAc. The org. layer is dried over MgS04, filtered, and the solvents are removed under reduced pressure. Purification of the crude by automated FC or by HPLC yields the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With tetrabutylammomium bromide; potassium carbonate In acetone at 20℃; for 3h; | Prepared according to general procedure 4 with K2CO3 (4.47 g, 32.3 mmol), 4-(chloromethyl)-1 ,2-difluorobenzene (1.05 g, 6.47 mmol), 5-nitro-1 H-pyrazole (731 mg, 6.47 mmol), and Bu4NBr (425 mg, 1.29 mmol) in acetone (45 mL). The reaction is complete after 3 h at rt. Purification of the crude by automated FC (Buchi, EtOAc / heptane 1 :99→ 5:95→ 10:90→ 15:85→ 25:75 → 35:65, 20 g silicagel, flow 20 mL/min) yields the title compound. LC-MS: tR = 0.83 min (conditions 3). General procedure 4 for the N-alkylation of 5-nitro-1H-pyrazole. K2CO3 or NaH is added to a sol. of 5-nitro-1 H- pyrazole in acetone or DMF or THF. The mixture is stirred for 15-30 min. The desired electrophile and Bu4NBr are added. The mixture is stirred efficiently at rt until the reaction is complete. The mixture is optionally filtered (if K2CO3 is used) or quenched with water (if NaH is used), and the filtrate is evaporated under reduced pressure. The residue is partitioned between water and EtOAc. The org. layer is dried over MgS04, filtered, and the solvents are removed under reduced pressure. Purification of the crude by automated FC or by HPLC yields the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With tetrabutylammomium bromide; potassium carbonate In acetone at 20℃; for 30h; | Prepared according to general procedure 4 with K2CO3 (3.18 g, 23.0 mmol), 4-fluoro-3,5-dimethylbenzyl bromide (1.00 g, 4.61 mmol), 5-nitro-1 H-pyrazole (521 mg, 4.61 mmol), and BmNBr (303 mg, 0.921 mmol) in acetone (45 mL). The reaction is complete after 30 h at rt. Purification of the crude by automated FC (Buchi, EtOAc / heptane 1 :99→ 5:95→ 10:90→ 15:85→ 25:75 → 35:65, 20 g silicagel, flow 20 mL/min) yields the title compound. LC-MS: tR = 0.90 min (conditions 3). General procedure 4 for the N-alkylation of 5-nitro-1H-pyrazole. K2CO3 or NaH is added to a sol. of 5-nitro-1 H- pyrazole in acetone or DMF or THF. The mixture is stirred for 15-30 min. The desired electrophile and Bu4NBr are added. The mixture is stirred efficiently at rt until the reaction is complete. The mixture is optionally filtered (if K2CO3 is used) or quenched with water (if NaH is used), and the filtrate is evaporated under reduced pressure. The residue is partitioned between water and EtOAc. The org. layer is dried over MgS04, filtered, and the solvents are removed under reduced pressure. Purification of the crude by automated FC or by HPLC yields the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With tetrabutylammomium bromide; potassium carbonate In acetone at 20℃; for 8h; | Prepared according to general procedure 4 with K2CO3 (3.51 g, 25.4 mmol), 4-fluoro-3-methylbenzyl bromide (1.03 g, 5.08 mmol), 5-nitro-1 H-pyrazole (574 mg, 5.08 mmol), and Bu4NBr (334 mg, 1.02 mmol) in acetone (45 mL). The reaction is complete after 8 h at rt. Purification of the crude by automated FC (Buchi, EtOAc / heptane 1 :99→ 5:95→ 10:90→ 15:85→ 25:75 → 35:65, 20 g silicagel, flow 20 mL/min) yields the title compound. LC-MS: tR = 0.86 min (conditions 3). General procedure 4 for the N-alkylation of 5-nitro-1H-pyrazole. K2CO3 or NaH is added to a sol. of 5-nitro-1 H- pyrazole in acetone or DMF or THF. The mixture is stirred for 15-30 min. The desired electrophile and Bu4NBr are added. The mixture is stirred efficiently at rt until the reaction is complete. The mixture is optionally filtered (if K2CO3 is used) or quenched with water (if NaH is used), and the filtrate is evaporated under reduced pressure. The residue is partitioned between water and EtOAc. The org. layer is dried over MgS04, filtered, and the solvents are removed under reduced pressure. Purification of the crude by automated FC or by HPLC yields the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | With N-chloro-succinimide In N,N-dimethyl-formamide at 90℃; Inert atmosphere; | 1 Example 1 4-chloro-3-nitro -1H-pyrazole (intermediate 2a) preparation Added to the reaction bottle 3-nitro -1H-pyrazole (5mmol), NBS (5.5mmol), adding 20mLDMF (N, N-dimethyl formamide), then heating to 90 °C, under the protection of nitrogen reaction sleepovers. After the reaction is complete, most of the DMF is removed by reduced pressure distillation, solid precipitating a large amount of water, filtering, 20 ml water washing, to obtain the target product solid after drying, light yellow solid. (Yield 87%) |
| 42% | With N-chloro-succinimide In N,N-dimethyl-formamide at 55℃; for 12h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | Stage #1: 3-nitro-1H-pyrazole With sodium t-butanolate In N,N-dimethyl-formamide at 0℃; for 0.333333h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 16h; | l-Methyl-3-nitro-l//-pyrazole . NaOtBu (19.11 g, 199.1 mmol) was added to a stirred solution of 3-nitro-lH-pyrazole (15 g, 132.7 mmol) in DMF (150 mL) at 0°C, and the reaction was stirred for 20 minutes. Mel (9.91 mL 159.24 mmol) was then added dropwise. The resulting mixture was stirred at RT for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was collected; washed with brine; dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography to afford 1 -methyl-3-nitro- 1 //-pyrazole (10 g, 59%) as an off white solid. TLC: 20% EtOAc/hexane (R 0.2). NMR (400 MHz, DMSO-de): d 7.98 (s, 1H), 7.03 (d, /= 2.0 Hz, 1H), 3.97 (s, 3H) ppm. |
| 20.7 g | With sodium t-butanolate In N,N-dimethyl-formamide at 0℃; for 3h; | 87 Step 1: 1-methyl-3-nitropyrazole Step 1: 1-methyl-3-nitropyrazole (0359) (0360) 3-nitropyrazole (20g, 0.177mol) and N, N-dimethylformamide (300mL) were added to a 1L reaction flask. The reaction mixture was stirred in an ice-salt bath for 20 minutes, and then sodium tert-butoxide (20.35g, 0.212mol) was slowly and carefully added in batches. The reaction mixture was stirred for 3 hours at 0°C. After completion of the reaction, excess saturated aqueous ammonium chloride solution was added to terminate the reaction, and then ethyl acetate was used to extract. The organic phase was washed with saturated aqueous sodium chloride solution, dried and concentrated to obtain the title compound (yellow solid, 20.7g, 92%), which was used directly for the next reaction. (MS: [M+1] none) |
| Stage #1: 3-nitro-1H-pyrazole With sodium t-butanolate In N,N-dimethyl-formamide at 0℃; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; | 1 l-Methyl-3-nitro-lH-pyrazole NaOtBu (19.11 g, 199.1 mmol) was added to a stirred solution of 3-nitro-lH-pyrazole (15 g, 132.7 mmol) in DMF (150 mL) at 0 °C, and the reaction was stirred for 20 minutes. To this solution was added Mel (9.91 mL 159.24 mmol) drop wise. The resulting reaction mixture was stirred at RT for 16 h. After completion, the mixture was quenched with water and extracted with ethyl acetate. The organic layer was collected; washed with brine; dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography to afford the title compound as an off-white solid. TLC: 20% EtOAc/hexane (R 0.2). H NMR (400 MHz, DMSO-76): 57.98 (s, 1H), 7.03 (d, 7 = 2.0 Hz, 1H), 3.97 (s, 3H). |
| Stage #1: 3-nitro-1H-pyrazole With sodium t-butanolate In N,N-dimethyl-formamide at 0℃; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; | 1 l-Methyl-3-nitro-lH-pyrazole NaOtBu (19.11 g, 199.1 mmol) was added to a stirred solution of 3-nitro-lH-pyrazole (15 g, 132.7 mmol) in DMF (150 mL) at 0 °C, and the reaction was stirred for 20 minutes. To this solution was added Mel (9.91 mL 159.24 mmol) drop wise. The resulting reaction mixture was stirred at RT for 16 h. After completion, the mixture was quenched with water and extracted with ethyl acetate. The organic layer was collected; washed with brine; dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography to afford the title compound as an off-white solid. TLC: 20% EtOAc/hexane (R 0.2). H NMR (400 MHz, DMSO-76): 57.98 (s, 1H), 7.03 (d, 7 = 2.0 Hz, 1H), 3.97 (s, 3H). | |
| 59 % | Stage #1: 3-nitro-1H-pyrazole With sodium t-butanolate In N,N-dimethyl-formamide at 0℃; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; | 1 l-Methyl-3-nitro-l/f-pyrazole . NaOtBu (19.11 g, 199.1 mmol) was added to a stirred solution of 3-nitro-lH-pyrazole (15 g, 132.7 mmol) in DMF (150 mL) at 0 °C, and the reaction was stirred for 20 minutes. Mel (9.91 mL 159.24 mmol) was then added dropwise. The resulting mixture was stirred at RT for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was collected; washed with brine; dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography to afford 1 -methy 1-3 -nitro- UT-pyrazole (10 g, 59%) as an off white solid. TLC: 20% EtOAc/hexane (R/ 0.2). *H NMR (400 MHz, DMSO-t/6): 8 7.98 (s, 1H), 7.03 (d, J= 2.0 Hz, 1H), 3.97 (s, 3H) ppm. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 51% 2: 11% | With potassium carbonate In dimethyl sulfoxide at 0 - 25℃; for 24h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 0.333333h; Stage #2: 4-chloropyrimidine hydrochloride In 1-methyl-pyrrolidin-2-one at 0 - 80℃; for 60h; | 1.1.1 Step 1: 4-(3-nitropyrazol-1-yl)pyrimidine [309] To a 0 °C solution of 3-nitro-1H-pyrazole (1.5 g, 13.27 mmol) in NMP (12.0 mL) was added NaH (1.2 g of 60 %w/w, 30.00 mmol). After 20 min, gas evolution slowed and reaction mixture was allowed to warm slowly to room temperature. The mixture was cooled back to 0 °C, and 4-chloropyrimidine (hydrochloride salt; 2.2 g, 14.57 mmol) was added. The resultant reaction mixture was heated to 80°C and stirred for 60 h. The reaction mixture was poured over ice with swirling, and a colorless precipitate formed. After standing for 16 h, the mixture was filtered, and the peach-colored solids were air-dried. The material was dissolved in hot ethyl acetate and then diluted with heptane to 50% ethyl acetate/heptane. The solution was chilled on ice, and the precipitated solid was collected by vacuum filtration and washed with heptanes to provide 4-(3-nitropyrazol-1-yl)pyrimidine (1.92 g, 74% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 1.3 Hz, 1H), 9.05 (d, J = 5.6 Hz, 1H), 8.98 (d, J = 2.9 Hz, 1H), 8.06 (dd, J = 5.6, 1.3 Hz, 1H), 7.41 (d, J = 2.9 Hz, 1H) ppm. ESI-MS m/z calc. 191.04, found 192.00 (M+1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 58% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 1.33333h; Stage #2: 3-chloropyridazine hydrochloride In 1-methyl-pyrrolidin-2-one at 0 - 80℃; for 16h; | 1.1.1 Step 1: 3-(3-nitro-1H-pyrazol-1-yl)pyridazine [320] To a 0 °C solution of 3-nitro-1H-pyrazole (1.5 g, 13.27 mmol) in NMP (1.2 mL) was added NaH (1.2 g of 60 %w/w, 30.00 mmol). After 20 minutes, the mixture was warmed to room temperature and stirred a further 60 min. The mixture was re-cooled to 0 °C and 3-chloropyridazine (hydrochloride salt; 2.0 g, 13.25 mmol) was added. The resultant mixture was heated to 80°C and stirred for 16 h. The reaction mixture was poured over ice, resulting in precipitation of a solid. The product was collected by vacuum filtration, and the solids air-dried to provide 3-(3-nitro-1H-pyrazol-1-yl)pyridazine (1.51 g, 58% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 9.38 (dd, J = 4.8, 1.4 Hz, 1H), 9.11 (d, J = 2.8 Hz, 1H), 8.32 (dd, J = 8.9, 1.4 Hz, 1H), 8.03 (dd, J = 8.9, 4.8 Hz, 1H), 7.43 (d, J = 2.8 Hz, 1H) ppm. ESI-MS m/z calc. 191.04, found 192.04 (M+1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 1.33333h; Stage #2: 2-fluoropyrimidine In 1-methyl-pyrrolidin-2-one at 0 - 80℃; for 16h; | 1.1.1 Step 1: 2-(3-nitro-1H-pyrazol-1-yl)pyrimidine [322] To a 0 °C solution of 3-nitro-1H-pyrazole (1.0 g, 8.84 mmol) in NMP (10.0 mL) was added NaH (425 mg of 60 %w/w, 10.63 mmol). After 20 minutes, the mixture was warmed to room temperature and stirred a further 60 minutes. The mixture was re-cooled to 0 °C and 2-fluoropyrimidine (1.0 g, 10.20 mmol) was added. The resultant mixture was heated to 80°C for 16 h. The reaction mixture was poured over ice, resulting in precipitation of a solid. The product was collected by vacuum filtration, and the solids air-dried to provide 2-(3-nitro-1H-pyrazol-1-yl)pyrimidine (1.66 g, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.00 (d, J = 4.8 Hz, 2H), 8.91 (d, J = 2.9 Hz, 1H), 7.68 (t, J = 4.9 Hz, 1H), 7.35 (d, J = 2.8 Hz, 1H) ppm. ESI-MS m/z calc. 191.04, found 191.96 (M+1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.0833333h; Inert atmosphere; Stage #2: ethyl iodide In N,N-dimethyl-formamide; mineral oil at 20 - 80℃; for 3h; Inert atmosphere; | |
| 66.1 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: ethyl iodide In N,N-dimethyl-formamide at 0 - 20℃; | Step 1: To a mixture of 3-nitro-1 H-pyrazole (4 g, 35.374 mmol) in DMF (10 mL) was added NaH (1.7 g, 70.833 mmol) at 0°C under nitrogen atmosphere. The resulting mixture was stirred at 0°C for 30 min. To the above mixture was added ethyl iodide (11 g, 70.721 mmol) at 0°C. The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography with 0-50% ethyl acetate in PE to afford 1-ethyl-3-nitropyrazole (3.3 g, 66.1%) as a yellow oil. MS m/z 142.1 [M+1]+ |
| 66.1 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: ethyl iodide In N,N-dimethyl-formamide at 0 - 20℃; | Step 1: To a mixture of 3-nitro-1 H-pyrazole (4 g, 35.374 mmol) in DMF (10 mL) was added NaH (1.7 g, 70.833 mmol) at 0°C under nitrogen atmosphere. The resulting mixture was stirred at 0°C for 30 min. To the above mixture was added ethyl iodide (11 g, 70.721 mmol) at 0°C. The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography with 0-50% ethyl acetate in PE to afford 1-ethyl-3-nitropyrazole (3.3 g, 66.1%) as a yellow oil. MS m/z 142.1 [M+1]+ |
| 66.1 % | Stage #1: 3-nitro-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: ethyl iodide In N,N-dimethyl-formamide at 0 - 20℃; | Step 1: To a mixture of 3-nitro-1 H-pyrazole (4 g, 35.374 mmol) in DMF (10 mL) was added NaH (1.7 g, 70.833 mmol) at 0°C under nitrogen atmosphere. The resulting mixture was stirred at 0°C for 30 min. To the above mixture was added ethyl iodide (11 g, 70.721 mmol) at 0°C. The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography with 0-50% ethyl acetate in PE to afford 1-ethyl-3-nitropyrazole (3.3 g, 66.1%) as a yellow oil. MS m/z 142.1 [M+1]+ |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | With potassium carbonate In acetonitrile at 45℃; for 24h; | A Synthesis of 1-isopropyl-3-nitro-1H-pyrazole I-1086 Potassium Carbonate [584-08-7] (59.9 g, 433.34 mmol) and 2-iodopropane [75-30-9] (28 mL, 1.7 g/ mL, 279.46 mmol) were added to a solution of 3-nitro-1H-pyrazole [26621-44-3] ( 10 45C for 24h. acetonitrile (3 stirred for 30 m . and MTBE (2:8). The solvent was removed in vacuo at 45C and co-distilled with MTBE at 45C. The crude product was allowed to stand for 12h to yield solid crystals. 15 The crystals were dissolved with heptane (124 mL) and stirred for 1.5 h at RT and the mixture was filtered and washed with heptane, and dried 4.5 h to yield 1-isopropyl-3- nitro-1H-pyrazole I-1086 (20.2 g, 73%) as a white solid |
| 68.2% | With potassium carbonate In acetonitrile at 25 - 65℃; for 136h; Large scale; | a Reaction Scheme 1 - Step a A 1.0 kilolitre clean and dry reactor was charged with acetonitrile (155 L) and 3-nitro- zH-pyrazole (1) (15.50 Kg) at 25-30 °C. Potassium carbonate (37.88 Kg) and 2-iodo- propane (24.46 Kg) were added to the reaction mixture at 25-30 °C. Then the temperature was raised to 40-45 °C and maintained at 40-45 °C for 24 hours. Then further 2-iodo-propane (2.33 Kg) was added to the reaction mixture at 40-45 °C and the reaction mixture was maintained at 40-45 °C for 96 hours. Then further 2-iodo- propane (3.49 Kg) and potassium carbonate (3.78 Kg) were added to the reaction mixture at 40-45 °C. Then the temperature was raised to 60-65 °C and maintained at 60-65 °C for 16 hours.The absence of 3 - n i t ro - z H- py r azo 1 e (1) was confirmed by HPLC (Limit: NMT 1.0 %). If, for a given run, the reaction mixture did not comply with the HPLC limit, it was maintained at 60-65 °C under stirring until the desired HPLC purity was achieved. After completion of the reaction, 80-90 % of the solvent was distilled off under vacuum at below 45 °C. A mixture of acetonitrile (31 L) and MTBE (124 L) (2:8) was charged to the reaction mixture and the reaction mixture was stirred for 30 minutes at 25-30 °C. The resulting salts were filtered and washed with a mixture of acetonitrile (15.5 L) and MTBE (62 L) (2:8) at 25-30 °C. The filtrate was distilled off completely at 45 °C. The resultant crude product was co-distilled with MTBE (15.5 L) at 45 °C and allowed to stand for 12 hours to afford solid crystals. The crystals were charged with heptane (124 L) and stirred for 1-2 hours at 25-30 °C. The reaction mixture was filtered, washed with heptane (31 L) at 25-30 °C, and dried in an air oven at 25-30 °C for 4-5 hours to afford the product. Final Product: i-isopropyl-3-nitro-iiT-pyrazole (2) Off white solid Output: 14.5 Kg Yield: 68.2 % Melting point: 45-48 °C lH NMR (DMSO-d6; 400 MHz): 1.45 (d, 6H), 4.65 (sept, lH), 7.06 (s, lH), and 8.12 (s, iH). MS: (M+H+) = 156.10 Moisture content (by Karl Fischer titration): HPLC purity: 98.61 % HPLC [X-bridge C18 column, 4.6 x 150 mm, 3.5 pm, mobile phase A = 10 mM ammonium bicarbonate in water, mobile phase B = acetonitrile, gradient programme (time/% B) = 0/10, 7/90, 15/90, 15.01/10; flow rate 1 mL per minute, temp = 25 °C): Rt = 6.11 minutes] |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | Stage #1: 3-nitro-1H-pyrazole With sodium carbonate In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: (S)-4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane In ethanol at 50℃; for 5h; Inert atmosphere; | 1.1 Step 1: Preparation of Intermediate (R)-: Under the protection of nitrogen, add 3-nitro-1H-pyrazole (1) (100.00g, 0.884mol),Ethanol (1.0L), sodium carbonate (133.90g, 1.26mol), the system is stirred at room temperature for 0.5h;(S)-(-)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane ((S)-2) (126.84g, 0.842mol) was dissolved and diluted with 634ml ethanol,Then start dropping into the reaction flask. After the addition was completed, the temperature was raised to 50°C and stirred for 5 hours.Distill under reduced pressure to remove ethanol, add (1.0L) water to dilute the residue, and then extract twice with dichloromethane (500ml x 2);The obtained organic phase was washed successively with water and saturated sodium chloride brine.Concentrate under reduced pressure to remove dichloromethane to obtain a crude oil;The crude product was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate mixed system) to obtain 166.5 g of light yellow oily product, The yield is 87%, and the ee value is ≥98%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 42% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 2h; | 84.1 Step 1: NaH (60% in mineral oil, 82.7 mg, 1.57 mmol, 4.5 equiv.) was added to a solution of 3-nitro-1H-pyrazole (79 mg, 0.70 mmol, 2 equiv.) in DMF (4 mL) at 0° C. and stirred at 0° C. for 10 min. The resulting mixture was added to a solution of 4-(bromomethyl)-3-methylpyridine hydrogen bromide salt (93 mg, 0.345 mmol, 1.0 equiv.) in DMF (4 mL) at 0° C. The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and concentrated in vacuo. The residue was purified by silica gel column chromatography (0-25% EtOAc (containing 1% Et3N) in DCM) to afford 3-methyl-4-((3-nitro-1H-pyrazol-1-yl)methyl)pyridine (32 mg, 42% yield) as a colorless film. LCMS: ESI-MS m/z: 219.1 [M+H]+. |
| 42% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 2h; | 84.1 Step 1: NaH (60% in mineral oil, 82.7 mg, 1.57 mmol, 4.5 equiv.) was added to a solution of 3-nitro-1H-pyrazole (79 mg, 0.70 mmol, 2 equiv.) in DMF (4 mL) at 0° C. and stirred at 0° C. for 10 min. The resulting mixture was added to a solution of 4-(bromomethyl)-3-methylpyridine hydrogen bromide salt (93 mg, 0.345 mmol, 1.0 equiv.) in DMF (4 mL) at 0° C. The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and concentrated in vacuo. The residue was purified by silica gel column chromatography (0-25% EtOAc (containing 1% Et3N) in DCM) to afford 3-methyl-4-((3-nitro-1H-pyrazol-1-yl)methyl)pyridine (32 mg, 42% yield) as a colorless film. LCMS: ESI-MS m/z: 219.1 [M+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 13.43 % | With caesium carbonate In N,N-dimethyl-formamide at 65℃; | 2 Step-2: To a solution of 3-nitro-1H-pyrazole (10 g, 88.44 mmol) and tert-butyl 4- methylsulfonyloxypiperidine-l-carboxylate (37.06 g, 132.66 mmol) in DMF (200 mL) was added cesium carbonate (86.44 g, 265.31 mmol) and the reaction was stirred for 16 hours at 65 °C. Then, the reaction mixture was quenched by water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the crude mixture was purified by column chromatography (30%-40% ethyl acetate in pet ether) to afford tert-butyl 4-(3- nitropyrazol-l-yl)piperidine-l-carboxylate (4 g, 11.88 mmol, 13.43% yield) as a white semiliquid. LC-MS (ES+): m/z 241.2 [[M-C(CH3)3]+H]+H]+. |
| 13.43 % | With caesium carbonate In N,N-dimethyl-formamide at 65℃; | Step-2: To a solution of 3-nitro-lH-pyrazole (10 g, 88.44 mmol) and tert-butyl 4-methyl sulfonyloxypiperidine-l-carboxylate (37.06 g, 132.66 mmol) in DMF (200 mL) was added cesium carbonate (86.44 g, 265.31 mmol) and the reaction was stirred for 16 hours at 65 °C. Then, the reaction mixture was quenched by water and extracted by ethyl acetate. The organic layer was concentrated under reduced pressure and the crude mixture was purified by column chromatography (30%-40% ethyl acetate in pet ether) to afford tert-butyl 4-(3- nitropyrazol-l-yl)piperidine-l-carboxylate (4 g, 11.88 mmol, 13.43% yield) as a white semi liquid. LC-MS (ES+): m/z 241.2 [[M-C(CH3)3]+H]+H]+. |
| 13.43 % | With caesium carbonate In N,N-dimethyl-formamide at 65℃; | Step-2: To a solution of 3-nitro-lH-pyrazole (10 g, 88.44 mmol) and tert-butyl 4-methyl sulfonyloxypiperidine-l-carboxylate (37.06 g, 132.66 mmol) in DMF (200 mL) was added cesium carbonate (86.44 g, 265.31 mmol) and the reaction was stirred for 16 hours at 65 °C. Then, the reaction mixture was quenched by water and extracted by ethyl acetate. The organic layer was concentrated under reduced pressure and the crude mixture was purified by column chromatography (30%-40% ethyl acetate in pet ether) to afford tert-butyl 4-(3- nitropyrazol-l-yl)piperidine-l-carboxylate (4 g, 11.88 mmol, 13.43% yield) as a white semi liquid. LC-MS (ES+): m/z 241.2 [[M-C(CH3)3]+H]+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61 % | With caesium carbonate In 1-methyl-pyrrolidin-2-one at 60℃; | 4 Step 4: tert-butyl 2-[2-(3-nitro-1H-pyrazol-1-yl)ethoxy]acetate To a mixture of 3-nitro-1H-pyrazole (500 mg, 4.42 mmol) and tert-butyl 2-{2-[(4-methylbenzenesulfonyl)oxy]ethoxy}acetate (1.46 g, 4.42 mmol) in NMP (10 mL) was added Cs2CO3 (1.44 g, 4.42 mmol) and the reaction was heated at 60 °C overnight. Once cooled, water (30 mL) was added, and the mixture was extracted with EtOAc (2 x 40 mL). The combined organics were washed with brine (2 x 40 mL), dried (MgSO4) and concentrated. The residue was purified by flash chromatography (0-50% EtOAc:heptane) to afford the title product (720 mg, 61%) as a yellow oil.1H NMR (300 MHz, CDCl3): 7.70 (d, J = 2.5 Hz, 1H), 6.88 (d, J = 2.5 Hz, 1H), 4.43 (t, J = 4.6 Hz, 2H), 3.96-3.92 (m, 4H), 1.46 (s, 9H). |
| 61 % | With caesium carbonate In 1-methyl-pyrrolidin-2-one at 60℃; | 4 Step 4: tert-butyl 2-[2-(3-nitro-1H-pyrazol-1-yl)ethoxy]acetate To a mixture of 3-nitro-1H-pyrazole (500 mg, 4.42 mmol) and tert-butyl 2-{2-[(4-methylbenzenesulfonyl)oxy]ethoxy}acetate (1.46 g, 4.42 mmol) in NMP (10 mL) was added Cs2CO3 (1.44 g, 4.42 mmol) and the reaction was heated at 60 °C overnight. Once cooled, water (30 mL) was added, and the mixture was extracted with EtOAc (2 x 40 mL). The combined organics were washed with brine (2 x 40 mL), dried (MgSO4) and concentrated. The residue was purified by flash chromatography (0-50% EtOAc:heptane) to afford the title product (720 mg, 61%) as a yellow oil.1H NMR (300 MHz, CDCl3): 7.70 (d, J = 2.5 Hz, 1H), 6.88 (d, J = 2.5 Hz, 1H), 4.43 (t, J = 4.6 Hz, 2H), 3.96-3.92 (m, 4H), 1.46 (s, 9H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 48 % | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; | Preparation 185: 3-[(3-nitropyrazol-1-yl)methyl]pyrrolidin-2-one. DEAD (40% solution in toluene, 2.2 mL, 4.9 mmol) was added to a solution of 3- (hydroxymethyl)pyrrolidin-2-one (520 mg, 4.5 mmol), 3-nitro-1H-pyrazole (460 mg, 4.1 mmol) and triphenylphosphine (1.3 g, 4.9 mmol) in THF (20 mL) at room temperature and stirred for 1 hour. The reaction mixture was concentrated in vacuo. The obtained residue 952-WO 115 was slurried in EtOAc (15 mL) at reflux for 5 minutes. The resultant suspension was cooled on ice and the precipitate was collected by filtration to afford the title compound as an off- white solid (412 mg, 48% yield). LCMS (METHOD 3) (ES): m/z 284.2 [M+H]+, RT = 0.64 min. 1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 2.6 Hz, 1H), 7.81 (s, 1H), 7.05 (d, J = 5 2.5 Hz, 1H), 4.48 (dd, J = 13.8, 4.7 Hz, 1H), 4.33 (dd, J = 13.8, 8.2 Hz, 1H), 3.18 - 3.06 (m, 2H), 2.87 (dtd, J = 9.7, 8.4, 4.7 Hz, 1H), 2.08 (dddd, J = 12.3, 8.7, 6.7, 3.2 Hz, 1H), 1.78 (ddt, J = 12.6, 10.4, 8.7 Hz, 1H). LCMS (METHOD 3) (ES): m/z 211.1 [M+H]+, RT = 0.37 min. |
| 48 % | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; | Preparation 185: 3-[(3-nitropyrazol-1-yl)methyl]pyrrolidin-2-one. DEAD (40% solution in toluene, 2.2 mL, 4.9 mmol) was added to a solution of 3- (hydroxymethyl)pyrrolidin-2-one (520 mg, 4.5 mmol), 3-nitro-1H-pyrazole (460 mg, 4.1 mmol) and triphenylphosphine (1.3 g, 4.9 mmol) in THF (20 mL) at room temperature and stirred for 1 hour. The reaction mixture was concentrated in vacuo. The obtained residue 952-WO 115 was slurried in EtOAc (15 mL) at reflux for 5 minutes. The resultant suspension was cooled on ice and the precipitate was collected by filtration to afford the title compound as an off- white solid (412 mg, 48% yield). LCMS (METHOD 3) (ES): m/z 284.2 [M+H]+, RT = 0.64 min. 1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 2.6 Hz, 1H), 7.81 (s, 1H), 7.05 (d, J = 5 2.5 Hz, 1H), 4.48 (dd, J = 13.8, 4.7 Hz, 1H), 4.33 (dd, J = 13.8, 8.2 Hz, 1H), 3.18 - 3.06 (m, 2H), 2.87 (dtd, J = 9.7, 8.4, 4.7 Hz, 1H), 2.08 (dddd, J = 12.3, 8.7, 6.7, 3.2 Hz, 1H), 1.78 (ddt, J = 12.6, 10.4, 8.7 Hz, 1H). LCMS (METHOD 3) (ES): m/z 211.1 [M+H]+, RT = 0.37 min. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 37 % | With tetrabutylammonium perchlorate; toluene-4-sulfonic acid In acetonitrile at 20℃; Electrochemical reaction; Further stages; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With di-tert-butyl (E)-azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With di-tert-butyl (E)-azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; | ||
| With caesium carbonate; copper(I) bromide In tetrahydrofuran at 120℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 4h; | General Procedure for the Synthesis of Intermediates 2a-2h General procedure: To a solution of 1 (1.0 equiv) in anhydrous DMF was added Cs2CO3 (1.2 equiv) and corresponding iodinated or brominated alkanes (1.2 equiv). The mixture was stirred at 60 °C for 4 h. When the reaction was deemed completed, the resulting mixture was quenched with water and extracted with ethyl acetate thrice. The combined organic phase was washed with water, brine, dried over anhydrous Na2SO4, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography to afford intermediates 2a-2h. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With potassium carbonate In dimethyl sulfoxide at 120℃; for 6h; | 1.1 Step 1 Synthesis of Compound 2 3-Nitropyrazole (1 g, 8.84 mmol), 2-chloro-6-difluoromethylpyridine (1.59 g, 9.73 mmol), and potassium carbonate (1.47 g, 10.6 mmol) were dissolved in dimethyl sulfoxide (10 mL) and stirred at 120°C for 6 hours. After cooling, water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was suspended in a hexane-ethyl acetate mixed solvent and filtered to obtain Compound 2 (1.53 g, yield 72%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: methyl 3,4-difluorobenzoate; 3-nitro-1H-pyrazole With potassium carbonate In dimethyl sulfoxide at 120℃; Stage #2: With potassium carbonate; methyl iodide In dimethyl sulfoxide for 2.3h; | 7.1 Step 1. Synthesis of methyl 3-fluoro-4-(3-nitro-1H-pyrazol-1-yl)benzoate (C25) A solution of 3-nitro-1H-pyrazole (925 mg, 8.18 mmol), methyl 3,4-difluorobenzoate (98%, 1.37 g, 7.80 mmol), and potassium carbonate (1.29 g, 9.33 mmol) in dimethyl sulfoxide (21 mL) was heated at 120° C. overnight, whereupon LCMS analysis indicated the presence of the corresponding carboxylic acid, from ester hydrolysis of C25 (LCMS m/z 250.2 [M-H]-). The reaction mixture was cooled to room temperature, treated with potassium carbonate (538 mg, 3.89 mmol) and iodomethane (0.485 mL, 7.79 mmol), and stirred for 2.3 hours, resulting in disappearance of the LCMS m/z 250.2 [M-H]- peak. The reaction mixture was then poured into water, and the resulting solid was collected by filtration to afford C25 as an off-white solid; this material was taken directly into the following step. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75% | With potassium carbonate In dimethyl sulfoxide at 120℃; | 13.1 Step 1. Synthesis of methyl 3-fluoro-2-methyl-4-(3-nitro-1H-pyrazol-1-yl)benzoate (C32) A mixture of 3-nitro-1H-pyrazole (95%, 339 mg, 2.87 mmol), methyl 3,4-difluoro-2-methylbenzoate (504 mg, 2.71 mmol), and potassium carbonate (450 mg, 3.26 mmol) in dimethyl sulfoxide (7.4 mL) was stirred overnight at 120° C., whereupon it was cooled to room temperature. Potassium carbonate (188 mg, 1.36 mmol) and iodomethane (0.254 mL, 4.08 mmol) were added and stirring was continued overnight at room temperature. The reaction mixture was then poured into water; the resulting solid was collected via filtration to provide C32 as a solid. Yield: 570 mg, 2.04 mmol, 75%. LCMS m/z 280.3 [M+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 40% | With pyridine; copper diacetate In 1,2-dichloro-ethane at 80℃; for 72h; Molecular sieve; | 14.1 Step 1. Synthesis of 1-[4-(benzyloxy)-3,5-difluorophenyl]-3-nitro-1H-pyrazole (C35) A suspension of 3-nitro-1H-pyrazole (320 mg, 2.83 mmol), [4-(benzyloxy)-3,5-difluorophenyl]boronic acid (97%, 847 mg, 3.11 mmol), copper(II) acetate (643 mg, 3.54 mmol), molecular sieves (4A, 1.6 mm diameter; 320 mg), and pyridine (0.412 mL, 5.09 mmol) in 1,2-dichloroethane (11.3 mL) was stirred at 80° C. for three days, whereupon LCMS analysis indicated conversion to C35: LCMS m/z 332.3 [M+H]+. After removal of solvent in vacuo, the residue was purified via silica gel chromatography (Gradient: 10% to 50% ethyl acetate in heptane), providing C35 as a white solid. Yield: 376 mg, 1.13 mmol, 40%. 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J=2.8 Hz, 1H), 7.85-7.75 (m, 2H), 7.47-7.33 (m, 6H), 5.24 (s, 2H). |
Tags: 26621-44-3 | 3-Nitropyrazole | Pyrazoles | Nitroes | Organic Building Blocks | Heterocyclic Building Blocks

A132966 [104599-37-3]
3,4-Dibromo-5-nitro-1H-pyrazole
Similarity: 0.70

A165614 [198348-89-9]
5-Nitro-3-pyrazolecarboxylic acid
Similarity: 0.68

A131082 [39846-84-9]
Ethyl 5-nitro-1H-pyrazole-3-carboxylate
Similarity: 0.62

A132966 [104599-37-3]
3,4-Dibromo-5-nitro-1H-pyrazole
Similarity: 0.70

A165614 [198348-89-9]
5-Nitro-3-pyrazolecarboxylic acid
Similarity: 0.68
Precautionary Statements-General | |
| Code | Phrase |
| P101 | If medical advice is needed,have product container or label at hand. |
| P102 | Keep out of reach of children. |
| P103 | Read label before use |
Prevention | |
| Code | Phrase |
| P201 | Obtain special instructions before use. |
| P202 | Do not handle until all safety precautions have been read and understood. |
| P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
| P211 | Do not spray on an open flame or other ignition source. |
| P220 | Keep/Store away from clothing/combustible materials. |
| P221 | Take any precaution to avoid mixing with combustibles |
| P222 | Do not allow contact with air. |
| P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
| P230 | Keep wetted |
| P231 | Handle under inert gas. |
| P232 | Protect from moisture. |
| P233 | Keep container tightly closed. |
| P234 | Keep only in original container. |
| P235 | Keep cool |
| P240 | Ground/bond container and receiving equipment. |
| P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
| P242 | Use only non-sparking tools. |
| P243 | Take precautionary measures against static discharge. |
| P244 | Keep reduction valves free from grease and oil. |
| P250 | Do not subject to grinding/shock/friction. |
| P251 | Pressurized container: Do not pierce or burn, even after use. |
| P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
| P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
| P262 | Do not get in eyes, on skin, or on clothing. |
| P263 | Avoid contact during pregnancy/while nursing. |
| P264 | Wash hands thoroughly after handling. |
| P265 | Wash skin thouroughly after handling. |
| P270 | Do not eat, drink or smoke when using this product. |
| P271 | Use only outdoors or in a well-ventilated area. |
| P272 | Contaminated work clothing should not be allowed out of the workplace. |
| P273 | Avoid release to the environment. |
| P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
| P281 | Use personal protective equipment as required. |
| P282 | Wear cold insulating gloves/face shield/eye protection. |
| P283 | Wear fire/flame resistant/retardant clothing. |
| P284 | Wear respiratory protection. |
| P285 | In case of inadequate ventilation wear respiratory protection. |
| P231 + P232 | Handle under inert gas. Protect from moisture. |
| P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
| Code | Phrase |
| P301 | IF SWALLOWED: |
| P304 | IF INHALED: |
| P305 | IF IN EYES: |
| P306 | IF ON CLOTHING: |
| P307 | IF exposed: |
| P308 | IF exposed or concerned: |
| P309 | IF exposed or if you feel unwell: |
| P310 | Immediately call a POISON CENTER or doctor/physician. |
| P311 | Call a POISON CENTER or doctor/physician. |
| P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
| P313 | Get medical advice/attention. |
| P314 | Get medical advice/attention if you feel unwell. |
| P315 | Get immediate medical advice/attention. |
| P320 | |
| P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
| P321 | |
| P322 | |
| P330 | Rinse mouth. |
| P331 | Do NOT induce vomiting. |
| P332 | IF SKIN irritation occurs: |
| P333 | If skin irritation or rash occurs: |
| P334 | Immerse in cool water/wrap n wet bandages. |
| P335 | Brush off loose particles from skin. |
| P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
| P337 | If eye irritation persists: |
| P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
| P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P342 | If experiencing respiratory symptoms: |
| P350 | Gently wash with plenty of soap and water. |
| P351 | Rinse cautiously with water for several minutes. |
| P352 | Wash with plenty of soap and water. |
| P353 | Rinse skin with water/shower. |
| P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
| P361 | Remove/Take off immediately all contaminated clothing. |
| P362 | Take off contaminated clothing and wash before reuse. |
| P363 | Wash contaminated clothing before reuse. |
| P370 | In case of fire: |
| P371 | In case of major fire and large quantities: |
| P372 | Explosion risk in case of fire. |
| P373 | DO NOT fight fire when fire reaches explosives. |
| P374 | Fight fire with normal precautions from a reasonable distance. |
| P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
| P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
| P378 | |
| P380 | Evacuate area. |
| P381 | Eliminate all ignition sources if safe to do so. |
| P390 | Absorb spillage to prevent material damage. |
| P391 | Collect spillage. Hazardous to the aquatic environment |
| P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
| P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
| P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
| P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
| P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
| P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
| P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
| P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
| P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
| P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
| P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
| P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
| P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
| P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
| P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
| P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
| P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
| P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
| P370 + P376 | In case of fire: Stop leak if safe to Do so. |
| P370 + P378 | In case of fire: |
| P370 + P380 | In case of fire: Evacuate area. |
| P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
| P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
| Code | Phrase |
| P401 | |
| P402 | Store in a dry place. |
| P403 | Store in a well-ventilated place. |
| P404 | Store in a closed container. |
| P405 | Store locked up. |
| P406 | Store in corrosive resistant/ container with a resistant inner liner. |
| P407 | Maintain air gap between stacks/pallets. |
| P410 | Protect from sunlight. |
| P411 | |
| P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
| P413 | |
| P420 | Store away from other materials. |
| P422 | |
| P402 + P404 | Store in a dry place. Store in a closed container. |
| P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
| P403 + P235 | Store in a well-ventilated place. Keep cool. |
| P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
| P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
| P411 + P235 | Keep cool. |
Disposal | |
| Code | Phrase |
| P501 | Dispose of contents/container to ... |
| P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
| Code | Phrase |
| H200 | Unstable explosive |
| H201 | Explosive; mass explosion hazard |
| H202 | Explosive; severe projection hazard |
| H203 | Explosive; fire, blast or projection hazard |
| H204 | Fire or projection hazard |
| H205 | May mass explode in fire |
| H220 | Extremely flammable gas |
| H221 | Flammable gas |
| H222 | Extremely flammable aerosol |
| H223 | Flammable aerosol |
| H224 | Extremely flammable liquid and vapour |
| H225 | Highly flammable liquid and vapour |
| H226 | Flammable liquid and vapour |
| H227 | Combustible liquid |
| H228 | Flammable solid |
| H229 | Pressurized container: may burst if heated |
| H230 | May react explosively even in the absence of air |
| H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
| H240 | Heating may cause an explosion |
| H241 | Heating may cause a fire or explosion |
| H242 | Heating may cause a fire |
| H250 | Catches fire spontaneously if exposed to air |
| H251 | Self-heating; may catch fire |
| H252 | Self-heating in large quantities; may catch fire |
| H260 | In contact with water releases flammable gases which may ignite spontaneously |
| H261 | In contact with water releases flammable gas |
| H270 | May cause or intensify fire; oxidizer |
| H271 | May cause fire or explosion; strong oxidizer |
| H272 | May intensify fire; oxidizer |
| H280 | Contains gas under pressure; may explode if heated |
| H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
| H290 | May be corrosive to metals |
Health hazards | |
| Code | Phrase |
| H300 | Fatal if swallowed |
| H301 | Toxic if swallowed |
| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
| H304 | May be fatal if swallowed and enters airways |
| H305 | May be harmful if swallowed and enters airways |
| H310 | Fatal in contact with skin |
| H311 | Toxic in contact with skin |
| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :
Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL




